The overall goal of this program project is to delineate the pathologic features of a chronic obstructive lung disease (COLD) resembling emphysema induced in the rat by exposure to NO2 and O3, separately and as a mixture. The epidemiologic importance of smoking in COLD has been established. The sequential morphometrics of the induction of emphysema with NO2 will be evaluated. Neonatal, pregnant, and nursing animals will be investigated as well by morphology, cytochemistry, and biochemical parameters, including lipids. Renewal studies on endothelial cells and interstitial macrophages will be conducted by autoradiography. The threshold effect in time and concentration of low atmospheric concentrations of the mixture of these oxidants will be determined also. Animals will be supplied from the core exposure facility, and observations by the various techniques will be correlated by the participants. Emphasis will be on specific mechanisms involved in the long-range development of reversible, progressive, and irreversible COLD.